{"doi":"10.3390/life13041015","title":"Overexpression of a Short Sulfonylurea Splice Variant Increases Cardiac Glucose Uptake and Uncouples Mitochondria by Regulating ROMK Activity","abstract":"The mitochondrial splice variant of the sulfonylurea receptor (SUR2A-55) is associated with protection from myocardial ischemia-reperfusion (IR) injury, increased mitochondrial ATP sensitive K+ channel activity (mitoKATP) and altered glucose metabolism. While mitoKATP channels composed of CCDC51 and ABCB8 exist, the mitochondrial K+ pore regulated by SUR2A-55 is unknown. We explored whether SUR2A-55 regulates ROMK to form an alternate mitoKATP. We assessed glucose uptake in mice overexpressing SUR2A-55 (TGSUR2A−55) compared with WT mice during IR injury. We then examined the expression level of ROMK and the effect of ROMK modulation on mitochondrial membrane potential (Δψm) in WT and TGSUR2A−55 mice. TGSUR2A−55 had increased glucose uptake compared to WT mice during IR injury. The expression of ROMK was similar in WT compared to TGSUR2A−55 mice. ROMK inhibition hyperpolarized resting cardiomyocyte Δψm from TGSUR2A−55 mice but not from WT mice. In addition, TGSUR2A−55 and ROMK inhibitor treated WT isolated cardiomyocytes had enhanced mitochondrial uncoupling. ROMK inhibition blocked diazoxide induced Δψm depolarization and prevented preservation of Δψm from FCCP perfusion in WT and to a lesser degree TGSUR2A−55 mice. In conclusion, cardio-protection from SUR2A-55 is associated with ROMK regulation, enhanced mitochondrial uncoupling and increased glucose uptake.","journal":"Life","year":2023,"id":374596,"datarank":0.24141568686511508,"base_score":1.6094379124341003,"endowment":1.6094379124341003,"self_citation_contribution":0.24141568686511508,"citation_network_contribution":0.0,"self_endowment_contribution":0.24141568686511508,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":4,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9542,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1136565,"name":"Holly Dooge","orcid":"0000-0003-4533-9713","position":1,"is_corresponding":false},{"id":1136955,"name":"Allison C. Wexler","orcid":null,"position":2,"is_corresponding":false},{"id":683160,"name":"Anna Kosmach","orcid":"0000-0002-9775-8058","position":3,"is_corresponding":false},{"id":1136956,"name":"Lara Serban","orcid":null,"position":4,"is_corresponding":false},{"id":1136957,"name":"Elizabeth A. Santos","orcid":null,"position":5,"is_corresponding":false},{"id":1057131,"name":"Francisco Alvarado","orcid":"0000-0003-0552-9029","position":6,"is_corresponding":false},{"id":476453,"name":"Timothy A. Hacker","orcid":"0000-0003-1473-1325","position":7,"is_corresponding":false},{"id":1136958,"name":"Mohun Ramratnam","orcid":null,"position":8,"is_corresponding":false},{"id":1136954,"name":"Sarah K. El-Meanawy","orcid":null,"position":0,"is_corresponding":true}],"reference_count":51,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T01:16:15.380731Z","pmid":"37109544","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}